FIGURE 6:

WDR62 mediates TNFα-induced JNK activation through MLK3. (A–D) WT and WDR62-KO cells were preincubated with the selective MLK3 inhibitors URMC-099 (100 nM) or CEP-1347 (50 nM) for 1 h and then treated with TNFα (50 ng/ml) for 15 min. (E–H) WT and WDR62-KO cells were preincubated with the selective TAK1 inhibitors 5Z-7-Oxozeaenol (20 nM) or takinib (2 µM) for 1 h then treated with TNFα (50 ng/ml) for 15 min. JNK activation was determined by Western blotting and densitometric analysis with p-JNK and JNK antibodies. The ratio of p-JNK/JNK obtained with TNFα-only treated WT cells was determined as 1 while the ratio obtained with all other treatments was determined relatively. Results are expressed as the mean ratio ± SEM of three independent experiments. *p ≤ 0.05, comparing pretreated to not pretreated cells of the same genotype; #p ≤ 0.05, comparing between WT and WDR62-KO counterparts.